Previous research has suggested that patients with classical Hodgkin lymphoma who are refractory to or relapse after first-line therapy may be more likely to be “cured” after receiving second-line salvage chemotherapy followed by autologous stem cell transplantation (ASCT) than after receiving standard-dose chemotherapy.1,2 High complete remission rates prior to ASCT have been shown to predict better long-term outcomes for patients with the condition.3 Researchers have investigated a number of combination therapy regimens as induction regimens prior to ASCT for refractory to or relapsed lymphoma, yielding pre-ASCT CR rates ranging from 20% to 54% and overall response rates (ORRs) of 60% to 80%.4
A prospective multicenter single-arm phase 2 study also indicated that the combination of bendamustine, gemcitabine, and vinorelbine (BEGEV) as second-line chemotherapy before ASCT, in 59 patients with relapsed/refractory (R/R) classical Hodgkin lymphoma, resulted in a CR of 73% and ORR of 83%.5
Now, updated 5-year results from that same study have confirmed the benefits, showing a CR rate of 75% and ORR of 83%.6 But experts cautioned that a randomized trial would be needed to determine whether the regimen is superior to other treatments.
“The update[d] 5-year results of BEGEV (bendamustine, gemcitabine, vinorelbine) followed by autologous stem cell transplantation in patients with Hodgkin disease refractory or relapsing to first-line therapy confirm the significant data in terms of CR rate (75%) as well as PFS (59%) and overall survival (78%),” lead study author Armando Santoro, MD, director of the Cancer Center at Humanitas Research Hospital, Milan, said in an email.
The trial involved 27 patients with classical Hodgkin lymphoma who were refractory to and 32 patients who relapsed after receiving 1 line of chemotherapy. The patients received 800 mg/m² gemcitabine on days 1 and 4, 20 mg/ m² vinorelbine on day 1, and 90 mg/m² bendamustine on days 2 and 3. The patients received 100 mg prednisolone on days 1 to 4. They were given 4 cycles of BEGEV every 21 days.
Those patients who experienced complete response or partial response after completing the 4 cycles received myeloablative therapy with carmustine, etoposide, cytarabine and melphalan or fotemustine, etoposide, cytarabine and melphalan, which preceded the reinfusion of CD341 cells.
The researchers evaluated disease responses before and after the fourth BEGEV cycle using computed tomography and 18F-fluorodeoxyglucose–positron emission tomography scans according to the International Working Group response criteria.
The treatment prompted CR in 44 patients (75%) and partial response (PR) in 5 (8%), yielding an OR of 83%. The authors noted that the CR rate was higher than the 54% CR rate previously reported for the ifosfamide, gemcitabine, vinorelbine, and prednisolone (IGEV) regimen as well as other second-line chemotherapy-based salvage regimens.
Of 49 patients who responded to BEGEV and were eligible for ASCT, 43 ended up receiving transplants. After 5 years following BEGEV treatment, the PFS for all series was 59% and OS was 78%. More than 90% of patients were at high risk for relapse post-ASCT. At 5 years, 33 patients who received transplants experienced continuous CR, 7 relapsed, and 3 died due to unrelated factors that included pneumonia, infection, and multiorgan failure.